Mashru R C, Sutariya Vijay B, Sankalia Mayur G, Sankalia Jolly M
Pharmacy Department, Faculty of Technology and Engineering, The M. S. University of Baroda, Gujarat, India.
Pharm Dev Technol. 2005;10(2):241-7. doi: 10.1081/pdt-54437.
The influence of drug concentration, pH in donor chamber, and 1-octanol/buffer partition coefficient on transbuccal permeation of ondansetron hydrochloride (pKa, 7.4) across porcine buccal mucosa was studied by using an in-line Franz type diffusion cell at 37 degrees C. The pH was adjusted to several values and the solubility of the drug in different pH was measured. Solubility of ondansetron hydrochloride decreases with increasing pH. The permeability of the drug was evaluated at different donor pH and drug concentrations. Permeability of un-ionized (Pu) and ionized (Pi) species of drug was calculated by fitting the data to a mathematical model. The steady state flux increased linearly with the donor concentration (r2 = 0.9843) at pH 7.4. The permeability coefficient and the partition coefficient of the drug increased with increasing pH. The values of Pu and Pi were 4.86 x 10(-6) cm/sec and 7.18 x 10(-7) (c)m/sec, respectively. The observed permeability coefficients and the permeability coefficients calculated from the mathematical model at various pH showed good linearity (r2 = 0.9799). The total permeability coefficient increased with increasing the fraction of un-ionized form of the drug. The drug permeated through buccal mucosa by a passive diffusion process. The non-ionized species of drug penetrated well through buccal mucosa and the permeation was a function of pH. Transbuccal delivery is a potential route for the administration of ondansetron hydrochloride.
采用在线Franz型扩散池，在37℃下研究了药物浓度、供体室pH值和1-辛醇/缓冲液分配系数对盐酸昂丹司琼（pKa为7.4）经猪颊黏膜透颊渗透的影响。将pH值调节至几个值，并测定药物在不同pH值下的溶解度。盐酸昂丹司琼的溶解度随pH值升高而降低。在不同的供体pH值和药物浓度下评估药物的渗透性。通过将数据拟合到数学模型来计算药物未电离（Pu）和电离（Pi）形式的渗透率。在pH 7.4时，稳态通量随供体浓度呈线性增加（r2 = 0.9843）。药物的渗透系数和分配系数随pH值升高而增加。Pu和Pi的值分别为4.86×10^(-6) cm/秒和7.18×10^(-7) cm/秒。在不同pH值下观察到的渗透系数与由数学模型计算得到的渗透系数显示出良好的线性关系（r2 = 0.9799）。总渗透系数随药物未电离形式比例的增加而增加。药物通过被动扩散过程透过颊黏膜。药物的非电离形式能很好地穿透颊黏膜，且渗透是pH值的函数。透颊给药是盐酸昂丹司琼给药的一种潜在途径。
